Ianalumab’s Road To Approval For Sjogren’s Looks Bumpier

TL;DR

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Two phase III trials of Novartis’ ianalumab met their primary disease-activity endpoint in patients with Sjögren’s disease, but the average benefit over placebo was small and key secondary outcomes were inconclusive. Novartis has begun another phase III trial, while the company’s plans and timing for regulatory applications remain unclear.

Two phase III trials of Novartis’ ianalumab met their primary endpoint in people with Sjögren’s disease, but the average improvement over placebo was small and several key symptom measures did not show a clear benefit. The full results, published in the New England Journal of Medicine, add uncertainty about whether the evidence will support approval; Novartis has started a further phase III trial.

The parallel trials, called NEPTUNUS-1 and NEPTUNUS-2, enrolled 779 patients in total. Both compared monthly ianalumab with placebo, while NEPTUNUS-2 also included a dosing group receiving treatment every three months. The main measure was change in the EULAR Sjögren’s Syndrome Disease Activity Index, or ESSDAI, after one year.

In the monthly-dose groups, average ESSDAI scores fell by 6.4 points in NEPTUNUS-1 and 6.5 points in NEPTUNUS-2. The corresponding placebo groups fell by 5.1 and 5.5 points. The resulting differences—1.3 and 1.0 points—were statistically significant in each trial, but the NEPTUNUS-1 result was close to the conventional significance threshold. The every-three-month dosing group did not differ from placebo on the primary measure.

The published report also describes weaker results on several secondary outcomes. The trials did not demonstrate clear advantages over placebo for important symptoms including dryness and salivation, and a responder analysis did not establish a clear difference in the share of patients achieving a five-point ESSDAI reduction. The investigators said the primary-endpoint effect was small and that there were no significant differences on key secondary outcomes. They and an accompanying editorial described the safety findings as not concerning.

Why the Mixed Results Matter

The findings present a mixed efficacy picture: both monthly-dose trials recorded statistically significant average changes in disease activity, but the difference from placebo was about one ESSDAI point. That distinction matters because statistical significance in a trial does not, by itself, show how noticeable or meaningful the benefit may be to patients.

The secondary results add to the uncertainty. Sjögren’s can affect symptoms such as dryness, salivary function and fatigue, yet the reported analyses did not show a consistent advantage across these measures. The results do not establish that ianalumab has no effect; they do leave questions about the size and practical importance of any benefit, and about whether the trial evidence is sufficient for regulatory review.

There is also a reason not to dismiss the primary findings outright. In an accompanying editorial, Simone Negrini of the University of Turin wrote that the similar estimates in two randomized populations make a drug effect more credible than a result from a single positive trial. He also stressed the small effect and the absence of definite effects on many other outcomes.

How NEPTUNUS Tested Ianalumab

Ianalumab is a biologic designed to inhibit B-cell activating factor, a protein involved in B-cell activity. The research rationale is linked to the role of B cells in Sjögren’s disease. The source report says the disease has no approved targeted therapies.

NEPTUNUS-1 randomized 275 patients between monthly ianalumab and placebo. NEPTUNUS-2 enrolled 504 and included a third, every-three-month dosing arm. Average ESSDAI scores at the start of the studies were about 12. Earlier conference results had indicated that both trials met their primary endpoint; the new journal publication provides a fuller account, including the secondary-outcome findings.

Novartis had previously indicated it planned to submit marketing applications early in 2026, then moved the timeline to the third quarter in its February annual report. The third quarter has passed, and the company had not clarified whether it submitted applications, according to the report.

“The effect was small and there were no significant differences”

— Thomas Grader-Beck, MD, and colleagues, reporting the trial findings

Approval Plans Remain Unconfirmed

Novartis has not confirmed, in the information reported, whether it submitted marketing applications after its revised third-quarter 2026 timeline. The published trial results alone do not settle how regulators may assess the evidence, or whether the company will seek approval on the basis of these studies.

It is also unclear whether the new study’s focus on patients with high symptom burden will produce stronger or more patient-relevant results. The report gives no completed findings from that trial. The absence of clear advantages on several secondary measures in NEPTUNUS should be distinguished from proof that the drug cannot benefit any subgroup.

THALASSA Will Test a New Group

Novartis has begun THALASSA, a placebo-controlled phase III trial in patients with Sjögren’s disease and high symptom burden. The study was first listed in May and is planned to enroll 570 participants; its estimated primary completion date is August 2029.

Further developments include the company clarifying whether it has filed for marketing authorization and any future regulatory decisions. THALASSA’s results will take longer to arrive, and could add evidence about ianalumab in the selected patient group. Until then, the published NEPTUNUS findings show statistically significant but small primary-endpoint differences alongside inconclusive results on several other measures.

Key Questions

Did ianalumab meet the main endpoint in the trials?

Yes. Both NEPTUNUS trials found a statistically significant average improvement in ESSDAI scores with monthly ianalumab compared with placebo after one year. The differences were 1.3 points and 1.0 point, respectively.

Do the results show that ianalumab will be approved?

No. The reported findings do not establish an approval outcome. Several secondary outcomes were inconclusive, and Novartis’ status on marketing applications was not clear in the report.

What is THALASSA?

THALASSA is a new placebo-controlled phase III trial of ianalumab in patients with Sjögren’s disease who have high symptom burden. It is planned to enroll 570 people, with primary completion estimated for August 2029.

Did the trials find a clear improvement in dryness or salivation?

The published report says the trials did not demonstrate clear improvement over placebo in important symptoms including dryness and salivation. Some measures showed numerical trends, but those did not establish a consistent benefit.

Source: rss